The cushioning function of large arteries encompasses distension during systole and recoil during diastole which transforms pulsatile flow into a steady flow in the microcirculation. Arterial stiffness, the inverse of distensibility, has been implicated in various etiologies of chronic common and monogenic cardiovascular diseases and is a major cause of morbidity and mortality globally. The first components that contribute to arterial stiffening are extracellular matrix (ECM) proteins that support the mechanical load, while the second important components are vascular smooth muscle cells (VSMCs), which not only regulate actomyosin interactions for contraction but mediate also mechanotransduction in cell-ECM homeostasis. Eventually, VSMC plasticity and signaling in both conductance and resistance arteries are highly relevant to the physiology of normal and early vascular aging. This review summarizes current concepts of central pressure and tensile pulsatile circumferential stress as key mechanical determinants of arterial wall remodeling, cell-ECM interactions depending mainly on the architecture of cytoskeletal proteins and focal adhesion, the large/small arteries cross-talk that gives rise to target organ damage, and inflammatory pathways leading to calcification or atherosclerosis. We further speculate on the contribution of cellular stiffness along the arterial tree to vascular wall stiffness. In addition, this review provides the latest advances in the identification of gene variants affecting arterial stiffening. Now that important hemodynamic and molecular mechanisms of arterial stiffness have been elucidated, and the complex interplay between ECM, cells, and sensors identified, further research should study their potential to halt or to reverse the development of arterial stiffness.

中文翻译：

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血管平滑肌细胞和动脉硬化：与发育，衰老和疾病的相关性。

大动脉的缓冲功能包括收缩期的扩张和舒张期的后坐力，从而将脉动流转化为微循环中的稳定流。动脉僵硬度是可扩张性的反面，已牵涉到慢性常见和单基因心血管疾病的各种病因中，并且是全球发病率和死亡率的主要原因。有助于动脉硬化的第一成分是支持机械负荷的细胞外基质（ECM）蛋白，而第二重要成分是血管平滑肌细胞（VSMC），不仅调节肌动球蛋白的相互作用来收缩，而且还介导细胞内的机械转导。 ECM动态平衡。最终，VSMC在导电性和阻力性动脉中的可塑性和信号传导与正常和早期血管衰老的生理高度相关。这篇综述总结了当前的中心压力和拉伸脉动圆周应力的概念，这些概念是动脉壁重塑，细胞-ECM相互作用的主要机械决定因素，主要取决于细胞骨架蛋白和粘着斑的结构，引起大/小动脉的相互干扰靶器官损伤以及导致钙化或动脉粥样硬化的炎症途径。我们进一步推测沿动脉树的细胞僵硬度对血管壁僵硬度的贡献。此外，本综述提供了鉴定影响动脉硬化的基因变异的最新进展。